Automatic analysis with fluid segmentation



July 31, 1962 G. KESSLER AUTOMATIC ANALYSIS WITH FLUID SEGMEN TATION Filed Dec.

W I o M "W United States Patent 3,047,367 AUTOMATIC ANALYSIS WITH FLUID SEGMENTATION Gerald Kessler, Tarrytown, N.Y., assignor to Technicon Instruments Corporation, Chauncey, N.Y., a corporation of New York Filed Dec. 1, 1959, Ser. No. 856,463 12 Claims. (Cl. 23-230) The present invention relates to automatic analysis and more particularly to such analysis which involves the use of a plurality of tubular conduits or passages of small internal diameters through which one or more liquids under analysis and one or more processing fluids are transmitted, respectively, in the operation of a quantitative analysis or monitoring system.

The invention is especially useful in its application to automatic continuous analysis apparatus of the type described, for example, in United States Patents Nos. 2,797,- 149 and 2,879,141, of the assignee of the present application, wherein streams of fluid are transmit-ted through the small tubular passages which are provided in such apparatus. As explained in said patents, air is injected into the liquid streams to divide them into a series of successive small segments separated from each other by intervening air segments or bubbles which serve to cleanse the internal walls of the passages; also air is introduced between successive samples of liquids under analysis to separate the samples from each other and to provide a cleansing action of the passages between successive samples in order to prevent contamination of one sample by another, which might otherwise occur due to the fiact that the samples are introduced into the passages in series one after the other in a flowing stream.

At a predetermined stage in the operation of the apparatus, it is necessary to abstract the air or other inert gas introduced into the liquid streams in order to consolidate and blend the liquid segments of the processed sample liquids into a continuous liquid stream for final examination, for example, in a colorimeter of the flow cell type or by spectral flame analysis as described, respectively, in the abovementioned patents and in the United States application of Leonard T. Skeggs, Serial No. 828,810, filed July 22, 1959, and assigned to the assignee of this application.

In accordance with the present invention and pursuant to one of the objects thereof, the use of air or other inert gas as the cleansing agent is dispensed with and replaced by a liquid, in order to obviate certain difliculties which may be encountered when air or other compressible fluids are employed as the cleansing agents. In this connection, it will be understood that in most instances, the use of air as the cleansing agent is to be preferred because it is highly elfective for this purpose and is readily available, without cost, from the ambient atmosphere. However, in certain processes, e.g., in spectral-flame analyses, the compressibility of air or other inert gas may result in pulsations of the liquid introduced into the spectral flame and thus cause the flame to flicker or be unsteady. This objectionable result is eliminated pursuant to this invention, since liquid is incompressible. This property of liquid, as the cleansing fluid, in eliminating or reducing pulsing of the liquid stream is aided by the resiliency of the walls of the tubing through which the liquids are pumped in the operation of the system. Also, it is sometimes necessary to use a cleansing fluid other than air because the oxygen in air may be a reactant in certain processes. In such case nitrogen or some other inert gas might be used, but an inert liquid according to this invention is preferred because of the difliculty in obtaining an inert gas in a pure state. Further, in the case of certain colorimetric analyses, liquid may be preferably used as the cleansing agent, instead of air, where 3,047,367, Patented July 31, 1962 ice foaming may be caused or exaggerated when air is used as the cleansing agent.

The above and other objects, features and advantages of the invention will be fully understood from the following description considered in connection with the accompanying illustrative drawings.

In the drawings:

FIG. 1 is a view illustrative of the method of the present invention in its application to automatic spectral-flame electric apparatus indicated schematically by the block 12 for controlling the operation of a recorder 14. Further description of this apparatus is unnecessary as it is not per se part of my invention. However, said apparatus is described by my assignees application Serial No. 837,401 filed September 1, 1959, in the name of Jack Isreeli as in-' ventor. The processed liquid under analysis, containing an internal standard, for example lithium nitrate in the case of analysis of blood serum for sodium or potassium, is supplied to the burner through tube 16 which is connected to the tube 18 of the burner which has an outlet opening at the base of the flame F. The combustible mixture, for example propane-oxygen, for the flame is supplied to the inlet 20 and passes through the tubular passage 22 around tube 16 to the burner tip 24.

A proportioning pump 26 is provided, as a module of the apparatus, for transmitting the sample and other liquids in the system. Briefly described, said pump comprises a plurality of resiliently flexible tubes, here shown as tube 28 for the sample liquid, tube 30 for a processing liquid, tube 32 for a cleansing liquid, tube 34 for a second processing liquid, tube 36 for a cleansing liquid, and tube 38 for aspirating cleansing liquid :from the system before the processed liquid is transmitted to tube 16 to the burner, in the manner hereinafter more particularly described. The proportioning pump is preferably of the construction described in my assignees US. Patent No. 2,893,324.

In the illustrated apparatus, a dialyzer 40 is employed. Said dialyzer is preferably of the construction described in my assignees U.S. Patent No. 2,864,507 immersed in a temperature-controlled heating bath indicated schematically by the block 42. Helical coils 44 and 46 are immersed in said bath and are connected respectively to the supply tubes 48 and 50, to which the above-mentioned pump tubes are connected, and to the dialyzer passages at the opposite sides of the membrane 52 of the dialyzer.

After dialysis, the fluid stream is discharged to waste from one side of the membrane through the outlet 54 while the segmented stream of the dialysate is pumped (from the other side of the dialyzer through the tube 56 into the inlet arm 58 of the separator 60. Said separator has an arm 62 through which the cleansing liquid segments indicated at CL in FIG. 3 are withdrawn from the liquid AL which is supplied to the burner 10 through tube 16 which is connected to the arm 64 of the separator. A tube 66 is connected to the outlet of separator arm 62 for conducting the separated liquid CL along with small quantites of the liquid under investigation to the pump tube 38. It will be understood that the relative flow rates of the fluids are controlled by the relative internal diameters of the pump tubes.

In accordance with the preferred mode of practicing the present invention, the cleansing liquid CL is lighter,

i.e., it has a lower specific gravity, than the processed liquid AL and therefore rises in the arm 62 which extends upwardly from the horizontal arms 58 and 64 of the separator. However, as illustrated in FIG. 4, the arm 62 may extend downwardly so that the heavier processed liquid flows downwardly through said arm to burner supply tube 16 while the lighter cleansing fluid CL fiows through the horizontally disposed arm 64 to the tube 66 for removal of the cleansing liquid from the system by the pump 26 through its pump tube 38.

The cleansing liquid is not only preferably lighter than the other liquids but is also immiscible therewith and inert thereto. As the present invention is applicable in a broad sense to the analysis of numerous liquids, it will be understood that the cleansing liquid selected in any particular case will be. one which is inert to the processed and processing liquids as will be readily understood and acted upon as a matter of course by those skilled in the art of chemistry and related fields. For example, in the present case where reference has been made to the analysis of blood serum, the serum containing lithium nitrate as an internal standard is dialyzed into distilled water which is supplied by pump tube 34, and the cleansing liquid which is supplied by pump tubes 32 and 36 is preferably an alcohol or a light mineral oil which is immiscible with water and the other substances involved in performing the process. In the particular illustration, i.e., the analysis of blood for sodium or potassium, I have employed isoamyl alcohol, with excellent results, as the cleansing liquid but it will be understood that other cleansing liquids are readily available and useful. It will be noted that the cleansing liquid is introduced into the stream of distilled water as well as into the stream of serum so that the stream of said cleansing liquid is present and active in the tubular passages at both sides of the membrane as well as in the passages leading to and from the dialyzer.

In the apparatus illustrated by FIG. 2, a colorimeter of the flow cell type and an associated photo-electric system schematically indicated by the block 12 are em ployed instead of a spectral-flame burner, for the analysis of various liquids in accordance with the inventions of the above-mentioned patents and patent application. In this case, the cleansing liquid is abstracted from the system before the processed liquid or dialysate is supplied to the flow cell 68 of the colorimeter. It will be understood that in FIG. 2 the pump tubes, other than the pump tube 38, are merely schematic of any one of an indefinite number of processing methods and are therefore not to be considered specific to a particular process.

It may be noted that the helical coils may serve as mixing coils or as coils of the heating bath 42 or both. Thus, in the method illustrated by FIG. 2, the coil 44 operates both as a mixing coil, to mix the lithium nitrate and the sample serum, and also to heat this liquid solution as well as the cleansing liquid to the temperature of the dialyzer. The dialyzer is preferably of the construction described in my assignees US. Patent No. Reissue 24,736. It will be understood that while the illustrated apparatus includes a dialyzer as a module thereof, the present invention is applicable as well to apparatus and methods which do not employ a dialyzer. Also, it will be understood that while the cleansing liquid is preferably lighter, as to specific gravity, than the liquid under analysis and the processing liquids, it is within the scope of this invention to employ a cleansing liquid which is heavier than said other liquids, and that in such case the horizontal arm 64 of the separator 60 in FIG. 3 or the vertical arm 62 in FIG. 4, would be connected to tube 66'while the vertical arm 62 in FIG. 1 and the horizontal arm 64- in FIG. 2 would correspondingly be connected to the inlet of the burner or colorimeter analyzer as the case might be.

While I have shown and described the preferred embodiment of my invention, it will be understood that the invention may be embodied other-wise than as herein spei cifically illustrated or described, and that certain changes in the form and arrangement of parts and in the specific manner of practicing the invention may be made without departing from the underlying idea or principles of this invention within the scope of the appended claims.

What is claimed is:

1. In an analyis method wherein a stream of liquid in a tubular passage is dialyzed into a second stream of liquid in a second tubular passage and thereby forming a stream of dialysate in a tubular passage, introducing into said second stream of liquid a stream of cleansing liquid immiscible with and inert to said dialysate and thereby forming a liquid stream comprising segments of dialysate separated from each other by segments of said cleansing liquid, abstracting said segments of cleansing liquid from said dialysate and concomitantly consolidating said segments of dialysate into a continuous liquid stream, and concurrently analyzing said continuous liquid stream with respect to a substance introduced therein by said dialysis from said first mentioned stream of liquid.

2. A method according to claim 1, wherein the cleansing liquid has a different specific gravity than said other liquids.

3. A method according to claim 1, wherein the cleansing liquid has a lower specific gravity than said other liquids.

4. In an analysis method wherein a stream of liquid in a tubular passage is dialyzed into a second stream of liquid in a second tubular passage and thereby forming a stream of dialysate in a tubular passage, introducing into said second stream of liquid a stream of cleansing liquid immiscible with and inert to said dialysate and thereby forming a liquid stream comprising segments of dialysate separated from each other by segments of said cleansing liquid, abstracting said segments of cleansing liquid from said dialysate and concomitantly consolidating said segments of dialysate into a continuous liquid stream, and concurrently introducing said continuous liquid stream into a spectral-flame for analyzing said continuous liquid stream with respect to a substance introduced therein by said dialysis from said first mentioned stream of liquid.

5. A method according to claim 4, wherein the cleansing liquid has a different specific gravity than said other liquids.

6. A method according to claim 4, wherein. the cleansing liquid has a lower specific gravity than said other liquids.

7. In an analysis method wherein a stream of liquid flows through a tubular passage; introducing into said tubular passage and concomitantly into said stream of liquid a stream of cleansing liquid immiscible with and inert to the liquid of said first mentioned stream and thereby forming a segmented liquid stream comprising a series of spaced liquid segments of said first mentioned liquid separated from each other by intervening segment of said cleansing liquid, said cleansing liquid having a specific gravity which is different from the specific gravity of said first mentioned liquid, removing said segments of said cleansing liquid from said segmented stream and concomitantly consolidating said segments of said first mentioned liquid into a continuous stream, and concurrently transmitting said continuous stream to an analyzer for analysis thereof in respect to a substance present in said first mentioned liquid.

8. In an analysis method wherein a stream of liquid flows through a tubular passage; introducing into said tubular passage and concomitantly into said stream of liquid a stream of a cleansing liquid immiscible with and inert to the liquid of said first mentioned stream and thereby forming a segmented liquid stream comprising a series of spaced liquid segments of said first mentioned liquid separated from each other by intervening segments of said cleansing liquid, said cleansing liquid having a specific gravity which is different from the specific gravity of said first mentioned liquid, removing said segments of said cleansing liquid from said segmented stream and concornitantly consolidating said segments of said first mentioned liquid into a continuous stream, and concurrently introducing said continuous stream into a spectral-flame for analysis thereof in respect to a substance present in said first mentioned liquid.

9. In an analysis method wherein a stream of liquid flows through a'tubular passage; introducing into said tubular passage and concomitantly into said stream of liquid a stream of a cleansing liquid immiscible with and inert to the liquid of said first mentioned stream and thereby forming a segmented liquid stream comprising a series of spaced liquid segments of said first mentioned liquid separated from each other by intervening segments of said cleansing liquid, said cleansing liquid having a specific gravity which is different from the specific gravity of said first mentioned liquid, removing said segments of said cleansing liquid from said segmented stream and concomitantly consolidating said segments of said first mentioned liquid into a continuous stream, and concurrently introducing said continuous stream into the flow 6 cell of a colorimeter for analysis thereof in respect to a substance present in said first mentioned liquid.

10. A method according to claim 7, wherein the cleansing liquid has a lower specific gravity than said first mentioned liquid.

11. A method according to claim 8, wherein the deans ing liquid has a lower specific gravity than said first mentioned liquid.

12. A method according to claim 9, wherein the cleansing liquid has a lower specific gravity than said first mentioned liquid. 7

References Cited in the file of this patent UNITED STATES PATENTS 2,189,950 Gump Feb. 13, 1940 2,196,176 Brigham Apr. 9, 1940 2,797,149 Skeggs June 25, 1957 2,899,280 Whitehead Aug. 11, 1959 2,933,293 Ferrari Apr. 19, 1960 

